Laub D N, Elmagbari N O, Elmagbari N M, Hausburg M A, Gardiner C S
Department of Biology, University of Northern Colorado, Greeley, Colorado 80639, USA.
Toxicol Sci. 2000 Jul;56(1):150-5. doi: 10.1093/toxsci/56.1.150.
This study investigated the effects of high doses of acetaminophen (APAP) on preimplantation embryos. Previous studies indicate that cleavage-stage embryos cannot synthesize reduced glutathione (GSH) de novo and may be sensitive to GSH-depleting toxicants. Alternatively, there may be maternal mechanisms that protect the embryos from the adverse effects of these toxicants. To address these possibilities, we cultured two-cell stage embryos in 0, 375, 750, or 1500 microM APAP and evaluated GSH concentration and development. APAP depressed embryo development to the morula and blastocyst stages in vitro, but a decrease in embryo GSH concentration was not detected. Furthermore, administration of 800 or 1430 mg/kg APAP to female mice 12 h prior to embryo collection on day 2 of gestation, or administration of 800 mg APAP/kg/day from day -8 to day 1 or day 3 of gestation, did not significantly affect ovary or embryo GSH concentration or embryo development. Liver GSH, however, was significantly decreased. Moreover, no adverse effects on embryo development to term were observed after treatment of female mice with 1430 mg APAP/kg/day from day -8 to day 3 of gestation. In summary, in vitro embryos were adversely affected, in terms of development, by APAP. In vivo, large doses of APAP depleted liver GSH but did not affect development of preimplantation embryos. In conclusion, preimplantation embryos appear to be protected from GSH-depleting toxicants such as APAP in vivo.
